Melanoma is a leading cause of morbidity in the human population. Australia has the highest rate of melanoma in the world. Melanoma is an aggressive skin cancer and is the third most common cancer in Australia for both men and women. It is predicted that one in thirty Australians have a form of melanoma resulting in the death of more than one thousand people per year in that country alone. When detected early most forms of melanoma can be effectively treated. However, the control of more advanced forms is less successful and an area of intensive research. A major goal in this area of research is the identification of molecules that are differentially expressed in benign and malignant melanocytic tumours that can be used for diagnosis and as targets for anti-cancer therapies (Kageshita T. et al; 1993).
Intercellular adhesion molecule-1 (ICAM-1), a crucial molecule in cellular inflammatory interactions, is an accepted melanoma progression antigen. Surface-expression of ICAM-1 on melanomas has been highly correlated with malignant melanoma progression (Kraus A. et al; 1997 and Morandini R. et al; 1998).
ICAM-1 is a member of the immunoglobulin (Ig) superfamily and a counter receptor for the integrin leucocyte function antigen-1 (LFA-11/CD11a) and Mac-(CD11b), and is a cellular attachment molecule for 90% of human rhinoviruses (Stuanton D. E., et al; 1989). In addition, ICAM-1 plays an important role in the pathogenesis of not only rhinovirus infection, but also in Plasmodium falciparum infection and in the exacerbations of asthma, chronic bronchitis and cystic fibrosis. Recently, complement regulatory proteins have been reported to be up-regulated on the surface of malignant melanomas, in particular decay-accelerating factor known as DAF (Cheung N K et al; 1998).
Viruses capable of inducing lysis of malignant cells through their replication process are known as oncolytic viruses and trials using oncolytic viruses to treat malignancies have been performed (Nemunaitis J; 1999). Most oncolytic viruses require proliferation in the same species or cell lineage. Infection of a cell by a virus involves attachment and uptake into the cell which leads to or is coincidental with uncoating of the viral capsid, and subsequently replication within the cell (Fenner F., et al. The Biology of Animal Viruses. Academic Press. New York, 1974 Second Ed.)
Oncolytic viruses assessed for capacity to kill cancer cells have included the adenovirus subtype Egypt 101 virus which showed oncolytic activity in the HeLa uterine/cervix cancer cell line, mumps virus for treatment of gastric carcinoma, uterine carcinoma and cutaneous carcinoma, Newcastle Disease Virus (NDV), influenza virus for treatment of ovarian cancer, and adenovirus for treatment of for instance, cervical carcinoma (Nemunaitis J; 1999). Other reports have indicated that adenoviruses and attenuated poliovirus recombinants may have use in the treatment of malignant glioma cells (Alemany R., et al 1999; Andreansky S. S., 1996), and that reovirus shows lytic capability in human U87 glioblastoma cells and NIH-3T3 cells with an activated Ras signalling pathway (Coffey M. C, et al, 1998; Strong J. E. et al, 1998).
In addition, a vaccinia oncolysate has been used in clinical trials to treat melanoma (Stage II) patients (Nemunaitis J., 1999). Modified, non-neurovirulent Herpes simplex viruses (HSV) have also been reported as showing promise for the treatment of brain tumours including intracranial melanoma, and subcutaneous human melanoma (Randazzo B. R., 1997), while adenovirus infection has been reported to enhance killing of melanoma cells by the plant mitotoxin, saporin (Satyamoorthy K., 1997).
The receptor on target cells recognised by adenovirus differs for different adenovirus types. That is, adenovirus subgroups A, C, D, E and F for instance recognise the CAR receptor while Adenovirus type 5 (subgroup C), Adenovirus type 2 (subgroup C) and Adenovirus type 9 (subgroup D) recognise major histocompatibility class II molecule, αmβ2 and αv integrins, respectively. The CAR receptor is known to be expressed on melanoma cell lines (Hemmi S., et al, 1998). Heparan sulfate is recognised by Herpes simplex types 1 and 2 and human herpes virus 7, Adeno-associated virus type 2. The receptor for human Herpesvirus 7 is CD4 while Epstein-Barr virus recognises complement receptor Cr2 (CD21). Poliovirus type 1 and 2 recognise poliovirus receptor (Pvr) for cell adhesion while reovirus recognises sialic acid. Influenza A and B virus recognise the sialic acid N-acetyl neuraminic acid for cell adhesion. In contrast, influenza type C virus recognises the sialic acid 9-O-acetyl neuraminic acid. Vaccina virus recognises both epidennal growth factor receptor and heparan sulfate. Coxsackievirus A13, A15 and A18 recognise ICAM-1 while A21 for instance recognises ICAM-1 and the complement regulatory protein DAF (CD55) (see eg. Shafren D. R., et al 1997). DAF is also recognised by Enterovirus 70. See for instance Flint S J, et al (2000) Principles of Virology:molecular biology, pathogenesis and control. ASM Press, Washington.
Metastatic tumour spread is a pathological process associated with a series of adhesion/de-adhesion events coupled with regulated tissue degradation. It is known that adhesion to and migration through the extracellular matrix is essential for tumour invasion. The largest family of extracellular adhesion molecules is the integrin family (Marshall J. F. and Hart I. R., 1996) and members of the αvβ group of integrins have been shown to be expressed on a variety of cell types. For instance αvβ1 is expressed on neuroblastoma, melanoma and osteosarcoma cells, αvβ3 is expressed on melanoma, glioblastoma and renal carcinoma cells, and αvβ5 is expressed on melanoma cells as is αvβ8 (Marshall J. F. and Hart I. R., 1996).
Despite progress being made in the treatment of malignancies, the treatment of cancer including melanoma presents a major challenge for research and there remains the need for alternatives to existing therapy approaches.